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Impaired Parahippocampal Gyrus–Orbitofrontal Cortex Circuit Associated with Visuospatial Memory Deficit as a Potential Biomarker and Interventional Approach for Alzheimer Disease

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Abstract

The parahippocampal gyrus–orbitofrontal cortex (PHG–OFC) circuit in humans is homologous to the postrhinal cortex (POR)–ventral lateral orbitofrontal cortex (vlOFC) circuit in rodents. Both are associated with visuospatial malfunctions in Alzheimer’s disease (AD). However, the underlying mechanisms remain to be elucidated. In this study, we explored the relationship between an impaired POR–vlOFC circuit and visuospatial memory deficits through retrograde tracing and in vivo local field potential recordings in 5XFAD mice, and investigated alterations of the PHG–OFC circuit by multi-domain magnetic resonance imaging (MRI) in patients on the AD spectrum. We demonstrated that an impaired glutamatergic POR–vlOFC circuit resulted in deficient visuospatial memory in 5XFAD mice. Moreover, MRI measurements of the PHG–OFC circuit had an accuracy of 77.33% for the classification of amnestic mild cognitive impairment converters versus non-converters. Thus, the PHG–OFC circuit explains the neuroanatomical basis of visuospatial memory deficits in AD, thereby providing a potential predictor for AD progression and a promising interventional approach for AD.

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Acknowledgements

We thank all participants in the study, without whom this research would not have been possible. This work was supported by the National Natural Science Foundation of China (81420108012, 81671046, 91832000, and 31700936), the Program of Excellent Talents in Medical Science of Jiangsu Province, China (JCRCA2016006), a Special Project of Clinical Medicine Science and Technology in Jiangsu Province, China (BL2014077), a Guangdong Province Grant (2017A030310496), Key-Area Research and Development Program of Guangdong Province, China (2018B030331001), a National Special Support Grant (W02020453), and Guangdong Provincial Key Laboratory of Brain Connectome and Behavior (2017B030301017).

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  1. Lin Zhu, Zan Wang and Zhanhong Du contributed equally to this work.

Authors and Affiliations

  1. Department of Neurology, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, 210009, China

    Lin Zhu, Zan Wang, Xinyang Qi, Hao Shu, Duan Liu, Fan Su, Qing Ye & Zhijun Zhang

  2. Shenzhen Key Laboratory of Neuropsychiatric Modulation, Guangdong Provincial Key Laboratory of Brain Connectome and Behavior, Chinese Academy of Science (CAS) Key Laboratory of Brain Connectome and Manipulation, the Brain Cognition and Brain Disease Institute (BCBDI), Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen, 518055, China

    Zhanhong Du, Xuemei Liu, Zheng Zhou, Yongqiang Tang, Ru Song & Liping Wang

  3. Laboratory Animal Center, Southeast University, Nanjing, 210009, China

    Xiaobin Wang

  4. Department of Neurology, Xuan Wu Hospital of Capital Medical University, Beijing, 100053, China

    Li Lin & Ying Han

  5. Department of Biophysics, Medical College of Wisconsin, Milwaukee, WI, 53226, USA

    Shijiang Li

  6. University of the Chinese Academy of Sciences, Beijing, 100049, China

    Liping Wang

  7. Beijing Institute of Geriatrics, Beijing, China

    Ying Han

  8. National Clinical Research Center for Geriatric Disorders, Beijing, China

    Ying Han

  9. Center of Alzheimer’s Disease, Beijing Institute for Brain Disorders, Beijing, China

    Ying Han

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  1. Lin Zhu
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Correspondence to Ying Han, Liping Wang or Zhijun Zhang.

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Zhu, L., Wang, Z., Du, Z. et al. Impaired Parahippocampal Gyrus–Orbitofrontal Cortex Circuit Associated with Visuospatial Memory Deficit as a Potential Biomarker and Interventional Approach for Alzheimer Disease. Neurosci. Bull. 36, 831–844 (2020). https://doi.org/10.1007/s12264-020-00498-3

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